Against a backdrop of rapidly changing social, economic and geopolitical settings and ideologies, the world is facing a wide range of challenges, including in biodiversity, climate, energy, the environment, food, health and water. These can only be addressed by fully harnessing key capacities that science offers. However, there is a crisis of trust in science which affects some sections of society and some policy-makers, impairing the capacity of science to deliver its essential roles. This damaged relationship between science, society and policy has immense health, economic and social consequences and implications for sustainability of the entire planet. Scientists must strive collectively to re-establish trust by society and politicians where it is damaged, and reinforce conviction of science's central importance in underpinning policy. Science's roles must in turn be acknowledged by policies that sustain innovation and freedom to work without political interference or constraints. A well-functioning and trusting relationship between science, society and policy-makers offers a potent means to thwart and mitigate emergent global challenges.